Prevalence of Barrett's esophagus in Lebanon.

BACKGROUND/AIMS: To determine the prevalence of Barrett's Esophagus (BE) in a tertiary care center in Lebanon and to compare IT with regional and global data. MATERIALS AND METHODS: All esophagogastroduodenoscopies (EGDs) performed between January 2003 and October 2013 at the American University of Beirut Medical Center (AUBMC) were reviewed, and cases of endoscopically suspected esophageal metaplasia (ESEM) were identified. Definite BE was considered only if histologically proven intestinal metaplasia was present. RESULTS: Totally, 16,787 patients underwent EGD; 219 patients (1.3%) were labeled as having ESEM. Only 41 patients had biopsyproven BE (18.7% of ESEM and 0.24% of total patients). The mean age of the patients with BE was 58.1 years [Standard deviation (SD) =13.7] and 78% were men. Of the 41 patients, 14 (34.1%) had long-segment BE (LSBE) (>3 cm) while 27 had short segment Barrett's Esophagus (SSBE) (≤3 cm). Hiatal hernia was identified in 54% of the patients, more commonly in those with LSBE. Only four patients had low-grade dysplasia, and none had high-grade dysplasia. CONCLUSION: The prevalence of BE in Lebanon is much lower than that in Western countries. The reasons for this East-West divide are unknown and require further investigation.

Aspirin Has a Protective Effect Against Adverse Outcomes in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

OBJECTIVE: To determine the effect of aspirin and anticoagulants on clinical outcomes and cause of in-hospital death in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). METHODS: Patients were identified from a tertiary center database that included all patients with UGIB. Clinical outcomes including (1) in-hospital mortality, (2) severe bleeding, (3) rebleeding, (4) in-hospital complications, and (5) length of hospital stay were examined in patients taking (a) aspirin only, (b) anticoagulants only, and (c) no antithrombotics. RESULTS: Of 717 patients with NVUGIB, 56 % (402) were taking at least one antithrombotic agent. Seventy-eight (11 %) patients died in hospital, and 310 (43 %) had severe bleeding (BP < 90 mmHg, HR > 120 b/min, Hb < 7 g/dL on presentation, or transfusion of >3 units). On multivariate analysis, being on aspirin was protective against in-hospital mortality [OR 0.26 (0.13-0.53)], rebleeding [OR 0.31 (0.17-0.59)], and predictive of a shorter hospital stay (coefficient = -4.2 days; 95 % CI -8.7, 0.3). Similarly, being on nonaspirin antiplatelets was protective against in-hospital mortality (P = 0.03). However, being on anticoagulants was predictive of in-hospital complications [OR 2.0 (1.20-3.35)] and severe bleeding [OR 1.69 (1.02-2.82)]. Compared to those not taking any antithrombotics, patients who bled on aspirin were less likely to die in hospital of uncontrolled gastrointestinal bleeding (3.6 vs 0 %, P ≤ 0.01) and systemic cancer (4.9 vs 0 %, P ≤ 0.002), but equally likely to die of cardiovascular/thromboembolic disease, sepsis, and multiorgan failure. CONCLUSION: Patients who present with NVUGIB on aspirin had reduced in-hospital mortality and fewer adverse outcomes, while those on anticoagulants had increased in-hospital complications.

Split-dose menthol-enhanced PEG vs PEG-ascorbic acid for colonoscopy preparation.

AIM: To compare the efficacy and palatability of 4 L polyethylene glycol electrolyte (PEG) plus sugar-free menthol candy (PEG + M) vs reduced-volume 2 L ascorbic acid-supplemented PEG (AscPEG). METHODS: In a randomized controlled trial setting, ambulatory patients scheduled for elective colonoscopy were prospectively enrolled. Patients were randomized to receive either PEG + M or AscPEG, both split-dosed with minimal dietary restriction. Palatability was assessed on a linear scale of 1 to 5 (1 = disgusting; 5 = tasty). Quality of preparation was scored by assignment-blinded endoscopists using the modified Aronchick and Ottawa scales. The main outcomes were the palatability and efficacy of the preparation. Secondary outcomes included patient willingness to retake the same preparation again in the future and completion of the prescribed preparation. RESULTS: Overall, 200 patients were enrolled (100 patients per arm). PEG + M was more palatable than AscPEG (76% vs 62%, P = 0.03). Completing the preparation was not different between study groups (91% PEG + M vs 86% AscPEG, P = 0.38) but more patients were willing to retake PEG + M (54% vs 40% respectively, P = 0.047). There was no significant difference between PEG + M vs AscPEG in adequate cleansing on both the modified Aronchick (82% vs 77%, P = 0.31) and the Ottawa scale (85% vs 74%, P = 0.054). However, PEG + M was superior in the left colon on the Ottawa subsegmental score (score 0-2: 94% for PEG + M vs 81% for AscPEG, P = 0.005) and received significantly more excellent ratings than AscPEG on the modified Aronchick scale (61% vs 43%, P = 0.009). Both preparations performed less well in afternoon vs morning examinations (inadequate: 29% vs 15.2%, P = 0.02). CONCLUSION: 4 L PEG plus menthol has better palatability and acceptability than 2 L ascorbic acid- PEG and is associated with a higher rate of excellent preparations; Clinicaltrial.gov identifier: NCT01788709.

Barrett esophagus: an update.

Many developments have been made in the field of Barrett esophagus that have tremendous clinical implications. There are new definitions of Barrett esophagus that have had an immediate clinical impact on cancer risk and screening. Of interest is the definition by the British Society of Gastroenterology, which does not require the presence of intestinal metaplasia for a diagnosis of Barrett esophagus. Imaging techniques that allow improved visualization of intestinal metaplasia at the cellular level are now being used in clinical practice. New hypotheses elucidating the progression from squamous epithelium to intestinal metaplasia have been proposed. Indeed, the crucial role that transcription factors have in the pathogenesis of Barrett esophagus has been clarified. Improved characterization of the molecular mechanisms underlying Barrett esophagus is an incentive to undertake more basic science research in this field. Such research could also help with the development of chemoprevention strategies for this precancerous condition. This Review discusses the advances in understanding of the pathogenesis, diagnosis and treatment of Barrett esophagus.

Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma.

BACKGROUND & AIMS: There is controversy over the outcomes of esophageal adenocarcinoma with superficial submucosal invasion. We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in patients with esophageal adenocarcinoma. METHODS: Pathology reports of esophagectomy samples collected from 1997 to 2007 were reviewed. Specimens from patients with esophageal adenocarcinoma and submucosal invasion were reviewed and classified as superficial (upper 1 third, sm1) or deep (middle third, sm2 or deepest third, sm3) invasion. Outcomes studied were presence of metastatic lymphadenopathy and overall survival. Variables of interest were analyzed as factors that affect overall and cancer-free survival using Cox proportional hazards modeling. A multivariate model was constructed to establish independent associations with survival. RESULTS: The study included 80 patients; 31 (39%) had sm1 carcinoma, 23 (29%) had sm2 carcinoma, and 26 (33%) had sm3 carcinoma. Superficial and deep submucosal invasion were associated with substantial rates of metastatic lymphadenopathy (12.9% and 20.4%, respectively). The mean follow-up time was 40.5 +/- 4 months and the mean overall unadjusted survival time was 53.8 +/- 4.1 months. Factors significantly associated with reduced survival time included the presence of metastatic lymph nodes (hazard ratio [HR], 2.89; confidence interval [CI], 1.13-6.88) and esophageal cancer recurrence (HR 6.39, CI 2.40-16.14), but not depth of submucosal invasion. CONCLUSIONS: Patients with sm1 esophageal carcinoma have substantial rates of metastatic lymphadenopathy. Endoscopic treatment of superficial submucosal adenocarcinoma is not advised for patients that are candidates for surgery.

Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus.

BACKGROUND: The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined. OBJECTIVE: To determine the rate and predictors of dysplasia/neoplasia recurrence after photodynamic therapy (PDT) in BE. SETTING: Retrospective analysis of a prospective cohort of BE patients seen at a specialized BE unit. METHODS: Patients underwent a standard protocol assessment with esophagogastroduodenoscopy and 4-quadrant biopsies every centimeter at 3-month intervals after ablation. Recurrence was defined as the appearance of any grade of dysplasia or neoplasia after 2 consecutive endoscopies without dysplasia. Entry histology, demographics, length of BE, presence and length of diaphragmatic hernia, EMR, stricture formation, nonsteroidal anti-inflammatory drug use, smoking, and the presence of nondysplastic BE or squamous epithelium were assessed for univariate associations. Time-to-recurrence analysis was done by using Cox proportional hazards regression. A multivariate model was constructed to establish independent associations with recurrence. RESULTS: A total of 363 patients underwent PDT with or without EMR. Of these, 261 patients were included in the final analysis (44 lost to follow-up, 46 had residual dysplasia, and 12 had no dysplasia at baseline). Indication for ablation was low-grade dysplasia (53 patients, 20%), high-grade dysplasia (152 patients, 58%), and intramucosal cancer (56 patients, 21%). Median follow-up was 36 months (interquartile range 18-79 months). Recurrence occurred in 45 patients. Median time to recurrence was 17 months (interquartile range 8-45 months). Significant predictors of recurrence on the multivariate model were older age (hazard ratio [HR] 1.04, P=.029), presence of residual nondysplastic BE (HR 2.88, P=.012), and a history of smoking (HR 2.68, P=.048). LIMITATIONS: Possibility of missing prevalent dysplasia despite aggressive surveillance. CONCLUSION: Recurrence of dysplasia/neoplasia after PDT ablation is associated with advanced age, smoking, and residual BE.

Barrett's esophagus: pathogenesis, treatment, and prevention.

Esophageal adenocarcinoma is the most common type of esophageal cancer seen in the United States and Western Europe. Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma and is believed to be found in 6% to 12% of patients undergoing endoscopy for gastroesophageal reflux disease and in more than 1% of all patients undergoing endoscopy. This article focuses on the pathogenesis, treatment, and prevention of BE.

Modulation of COX-2 expression by statins in human monocytic cells.

Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and thromboxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reductases and cholesterol synthesis, which block the expression of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2 induction in human monocytic cell line U937 and analyzed the underlying mechanisms. Pretreatment of U937 cells with simvastatin or mevastatin for 24 h resulted in a significant reduction in the lipopolysaccharide (LPS)-dependent induction of prostaglandin E2, thromboxane A2 synthesis, and COX-2 expression. Mevalonate, the direct metabolite of HMG CoA reductase, and farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, intermediates of the mevalonate pathway, significantly reversed the inhibitory effect of statins on COX-2. An inhibitor of geranylgeranyl transferases, GGTI-286 mimicked the effect of statins on COX-2 expression. Cytonecrotic factor-1 increased LPS-dependent expression of COX-2. Treatment of cells with NSC 23766, an inhibitor of Rac, which we demonstrated to block Rac 2 activation, resulted in an inhibition of the LPS-dependent expression of COX-2. Whereas no effect was obtained with RhoA/C blocker, C3 exoenzyme. Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. In macrophages, the antiinflammatory effects of statins are mediated in part through the inhibition of COX-2 and prostanoids. Rac GTPase protein is identified as one of the targets of statins in this regulation.

Ceramide inhibits IL-2 production by preventing protein kinase C-dependent NF-kappaB activation: possible role in protein kinase Ctheta regulation.

The role of the sphingolipid ceramide in modulating the immune response has been controversial, in part because of conflicting data regarding its ability to regulate the transcription factor NF-kappaB. To help clarify this role, we investigated the effects of ceramide on IL-2, a central NF-kappaB target. We found that ceramide inhibited protein kinase C (PKC)-mediated activation of NF-kappaB. Ceramide was found to significantly reduce the kinase activity of PKCtheta as well as PKCalpha, the critical PKC isozymes involved in TCR-induced NF-kappaB activation. This was followed by strong inhibition of IL-2 production in both Jurkat T leukemia and primary T cells. Exogenous sphingomyelinase, which generates ceramide at the cell membrane, also inhibited IL-2 production. As expected, the repression of NF-kappaB activation by ceramide led to the reduction of transcription of the IL-2 gene in a dose-dependent manner. Inhibition of IL-2 production by ceramide was partially overcome when NF-kappaB nuclear translocation was reconstituted with activation of a PKC-independent pathway by TNF-alpha or when PKCtheta was overexpressed. Importantly, neither the conversion of ceramide to complex glycosphingolipids, which are known to have immunosuppressive effects, nor its hydrolysis to sphingosine, a known inhibitor of PKC, was necessary for its inhibitory activity. These results indicate that ceramide plays a negative regulatory role in the activation of NF-kappaB and its targets as a result of inhibition of PKC.